Preparation of thiosulfenamides



United States Patent 3,147,256 PREPARATION 0F THIOSULFENAMIDES Marlyn J.Brock, Akron, and George D. Louth, Doylestown, Ohio, assignors to TheFirestone Tire & Rubber Company, Akron, Ohio, a corporation of Ohio NoDrawing. Filed May 20, 1959, Ser. No. 814,390 Claims. (Cl. 260247.1)

This invention relates to the preparation of thiosulfenamides.Thiosulfenamides are powerful accelerators and curing agents for thevulcanization of natural rubber and the synthetic, sulfur-vulcanizablediene rubbers. These accelerator-curing agents are especially useful inpneumatic tire tread stocks, in which a powerful but delayedaction,non-scorching, curing combination is needed for successful factoryprocessing of the stocks.

The compounds produced in accordance with the present invention arethiosulfenamides, represented by the formula in which A stands for athiazole, thiazoline, oxazole, irnidazole or imidazoline radical, R andR are the same or different aliphatic, cycloaliphatic or aralkyl groupsor R and R together form a single chain (which can contain -CH -O-, NHor S) constituting with the attached nitrogen atom a heterocyclicradical, and R can be hydrogen.

The invention provides a new method of making such thiosulfenamides byinteracting an azole mercaptan (ASH) and a primary or secondary aminewith a sulfur halide, preferably sulfur dichloride. The course of thepreparation reaction can be represented as follows:

A-SH NH SuX X represents chlorine or bromine. When SCl is employed, nofree sulfur is obtained. It is desirable to neutralize the halogen acidformed in the reaction by adding either initially or during the courseof the reaction some acid-binding substance, such as excess R(R )NH,ammonia, an alkali metal hydroxide, an alkaline earth metal hydroxide orany of the well known alkaline reacting salts or other compounds whichdo not compete with the amine employed for coupling to the disulfidelinkage. The mercaptan and the amine can be initially reacted to formthe amine salt, and the latter can then be reacted with the sulfurhalide in the presence of an alkaline substance. Also an inorganic saltof the mercaptan (formed by reacting the mercaptan with ammonia, analkali metal hydroxide, an alkaline earth metal hydroxide, etc.) can bereacted with the amine and the sulfur halide, and an additional mole ofacid-fixing substance added initially or during the reaction.

Having generally described the invention, the following examples arepresented for purposes of illustration.

Example 1 One-tenth mole (17 grams) of Z-mercaptobenzothiazole wasdispersed in 250 ml. of chloroform in a 500 ml., 3-neck flask fittedwith a stirrer and a reflux condenser. To the continuously stirredmixture 0.3 mole (27 grams) of morpholine was added and the flask wasimmersed in an ice bath. One-tenth mole (10 grams) of sulfur dichloridewas added dropwise and stirring was continued for one-half hour. Theprecipitated amine hydrochloride was filtered oif and the filtrate wasevaporated to dryness. The dry residue was washed with water and thenwith a little ether. Twenty-five and one-half grams of product (Mll27129 C.) was obtained which constituted 90% of the theoretical yield.The product was identified as N-morpholinylbenzothiazole 2thiosulfenamide by X-ray diffraction techniques; its X-ray diagram wassubstantially identical to that of an authentic sample of this compoundprepared by a known method.

Example 2 One-hundredth mole (1.9 grams) of the sodium salt ofZ-mercaptobenzothiazole was dissolved in 3.4 grams of morpholine and asmall amount of water was added to produce a solution. Chloroform wasthen added with care being taken not to cause precipitation.One-hundredth mole of sulfur dichloride (0.65 ml.) was dissolved inchloroform and slowly added. The resulting solution was evaporated todryness. The solid obtained was washed with ether and water. The producthad a melting point of 127-l29 C. and was identified by X-raydiffraction as N-rnorpholinylbenzothiazole-Z-thiosulfenamide.

Example 3 Four-tenth mole (34- grams) of piperidine and 200 ml. ofchloroform were placed in a flask, and the solution was cooled in an icebath. One-tenth mole (10 grams) of sulfur dichloride was diluted to 40ml. with chloroform and the solution was added dropwise to the flaskwith constant stirring. Stirring was continued for about five minutesfollowing addition of the sulfur dichloride solution, whereupon 0.1 mole(17 grams) of 2-mercaptobenzothiazole dispersed in ml. of chloroform wasslowly added. After it had been stirred for about 15 minutes, thesolution was transferred to a crystallizing dish and allowed toevaporate spontaneously. The residual product was washed with water andether. The air-dried product was characterized by a melting point of84-85 C. and was analyzed for sulfur, hydrogen and carbon with thefollowing results:

Found: percent S, 33.95; percent C, 50.74; percent H, 5.00. Calculatedfor C H N S percent S, 34.04; percent C, 51.06; percent H, 4.96.

The ultra-violet absorption characteristics of the product establishedthe presence of adisulfide linkage. The X-ray diifraction diagram of theproduct was different from that of the reactants, the amine salt andalso different from that of 2,2'-dithio-bis-benzothiazole. The productwas thus identified as Npiperidinylbenzothiazole-Z- thiosulfenamide.

Example 4 Fifty ml. of chloroform was placed in a flask and cooled in anice bath. Dirnethylamine gas was bubbled through the chloroform for fourminutes and 0.01 mole (1.7 grams) Z-mercaptobenzothiazole was then addedwith vigorous stirring. Sulfur dichloride (l ml.'diluted to 5 ml. withchloroform) was then added. Additional dimethylamine gas was thenbubbled through the solution until it was judged that no more gas wasabsorbed. Stirring was then continued for 10 minutes. The chloroformsoluiton was extracted three times with water, dried with sodiumsulfate, filtered, and evaporated to dryness. The solid product meltedat 96-98 C. The ultra-violet absorption curve established the presenceof a disulfide linkage. The product, in 81% yield, was N,N-dimethyl-2-benzothiazole thiosulfenamide, the X-ray diagram of which wasdifferent from that of the reactants, the amine salt and also2,2'-dithio-bis-benzothiazole.

Example 5 Twenty-seven grams of liquid dimethylamine was dissolved in500 ml. of chloroform, the temperature being maintained in a water bathat 13 C. A slurry of 34 grams of Z-mercaptobenzothiazole in chloroformwas added and the resulting solution was stirred for minutes, at whichtime the temperature rose to 17 C. Twenty grams of sulfur dichloridedissolved in chloroform was slowly added. The temperature of theresulting mixture was 25 C. The mixture was stirred for two hours morewith the temperature being maintained at about 20 C. The chloroformsolution was then washed several times with water by agitation in aWaring Blendor until the last wash water had a pH of approximately 8.The solution was then dried with sodium sulfate, treated with activatedcharcoal and then allowed to evaporate to dryness. The residue was takenup in ether, recrystallized from ether and air dried. The productweighed 20 grams and was characterized by a melting point of 69-70 C.The X-ray diffraction pattern established that the product was the sameN,N-dimethyl-2-benzothiazole thiosulfenamide obtained in Example 4.

Example 6 Two hundred and fifty ml. of chloroform was placed in a flaskand chilled to 30 C. by means of solid CO A dimethylamine cylinder wasinverted and 13.5 grams of the liquid was weighed into a beaker andimmediately added to the chloroform in the reaction vessel. Seventeengrams of 2-mercaptobenzothiazole was added with vigorous stirring. Tengrams of sulfur dichloride was diluted to 25 ml. with chloroform andadded dropwise to the mercaptobenzothiazole-chloroform solution in theflask. Stirring was continued for about minutes, and the chloroformsolution was then washed with water until the pH of the solution wasnearly 7.0. The solution was dried with sodium sulfate and evaporated at40 C. The residue was treated with diethyl ether and filtered. Theether-insoluble fraction was established by X-ray diffraction to be2,2-dithio-bis-benzothiazole. The ether-soluble fraction was establishedby X-ray diffraction to be the same product as that obtained in Examples4 and 5. A sample was subjected to analysis for nitrogen and sulfur,with the following results:

Example 7 One-hundredth mole (1.7 grams) of Z-mercaptobenzothiazole wasdispersed in ml. of chloroform, and 0.03 mole (2.6 grams) of morpholinewas stirred in. Then 0.01 mole (1.4 grams) of sulfur monochloride wasdiluted with 5 ml. of chloroform and added dropwise, with constantstirring to the mixture of the azole and amine. After completion of thereaction the precipitated amine hydrochloride was removed by filtrationand washed with chloroform. The combined filtrates were evaporated atroom temperature. The residue was washed with three portions of waterand then with three portions of ether and then allowed to dry. An X-raydiagram of the residue showed it to be substantially identical with thatof the N-morpholinyl-Z-benzothiazole thiosulfenamide of Examples 1 and2.

Example 8 One-hundredth mole (1.7 grams) of Z-mercaptobenzothiazole and3 grams (0.03 mole) of cyclohexylamine were dissolved in 15 ml. ofchloroform. Sulfur dichloride (0.65 ml., 0.01 mole) was added slowlywith stirring. The solution was cooled during the reaction. At thecompletion of the reaction a small amount of solid .4 had formed. Uponevaporation of the solvent a yellow solid product was obtained. Thissolid was washed with water to remove the amine hydrochloride. A stickysolid remained, and this was purified by washing it with ether. Thefinal product was a yellow crystalline solid melting at 128- 132" C.,the X-ray diffraction diagram of which was substantially different fromthe X-ray diagrams of the starting materials, the amine salt,2,2'-dithio-bisbenzothiazole and N-cyclohexylbenzothiazole-Z-sulfenamide. Therefore the product wasN-cyclohexyl-Z-benzothiazole thiosulfenamide of the formula Morpholine(23 grams, 0.25 mole) and Z-mercaptobenzothiazole (42 grams, 0.25 mole)were dissolved in 500 ml. of chloroform. A solution of sodium hydroxide(22 grams, 0.5 mole+l0% excess) in 150 ml. of water was added, formingtwo phases in the reaction vessel. Sulfur dichloride (26 grams, 0.25mole) in ml. of chloroform was added dropwise with stirring. Thetemperature of the reaction mixture was maintained at 30-40 C. by meansof an ice bath. The mixture was stirred for an additional 30 minutesfollowing the sulfur dichloride addition. Then the chloroform layer wasseparated and washed with water. The solvent was thereafter allowed toevaporate at room temperature. The dried product (43 grams) melted atl22126 C. A mixed melting point with a known sample ofN-morpholinylbenzothiazole-Z-thiosulfenamide (M.P. 129-130 C.) was -128C. X-ray analysis of the product showed it to be substantiallyN-morpholinylbenzothiazole-2-thiosulfenamide with a small amount of2,2-dithio-bis-benzothiazole as an impurity.

Other amines can be utilized in the invention in addition to thosedisclosed above, as follows:

Diethylamine Di-n-propylamine Di-n-butylamine Di-isobutylamineDi-n-amylamine Di-isoamylamine Di-n-hexylamine Di-n-heptylamineDi-n-octylamine Dibenzylamine Methyl cyclohexylamine Ethylcyclohexylamine Thiomorpholine 4-N-ethylpiperazine PyrrolidineIsopropylamine t-Butylamine tt-Octylamine l-methyl-cyclohexylaminel-ethyl-cyclohexylamine l-methyl-cyclopentylamine Thus the aminesemployed in the invention are represented by the formula N-H R1 whereinthe Rs are the same or different aliphatic, cycloaliphatic or aralkylradicals, R can be hydrogen, and R and R can be joined to form a singlechain (which can contain CH O--, NH or --S-) constituting with theattached nitrogen atom a heterocyclic radical. The mercapto azoles whichcan be used include the mercaptothiazoles, mercaptoirnidazoles and themercaptooxazoles. Either aliphatic or aromatic azoles can be used.

Representative examples are Z-mercaptothiazole Z-mercaptooxazoleZ-mercaptoimidazole 2-mercapto-4-methylthiazole2-mercapto-4-methyloxazole 2-mercapto-4-methylimidazole2-mercapto-4-ethylthiazole Z-mercapto-4-n-propylthiazole2-mercapto-4-n-propyloxazole 2-mercapto-4-n-propylimidazole2-mercapto-4-n-butylthiazole 2-rnercapto-4-n-butyloxazole2-mercapto-4-n-butylimidazole 2-mercapto-4,S-dimethylthiazole2-mercapto-4,S-dimethyloxazole 2-mercapto-4,S-dimethylimidazoleZ-mercapto-4,5-diethylthiazole 2-mercapto-4,5-diethyloxazole2-mercapto-4,S-diethylimidazole 2-mercapto-4,S-di-n-propylthiazoleZ-mercapto-4,5-di-n-propyloxazole 2-mercapto-4,5-di-n-propylimidazole2-mercapto-4,5-di-n-butylthiazole 2-mercapto-4,S-di-n-butyloxazole2-mercapto-4,5-di-n-butylimidazole 4-phenyl-2-mercaptothiazole4-phenyl-2-mercaptooxazole 4-phenyl-2-mercaptoimidazole4-phenyl-5-methyl-2-mercaptothiazole4-phenyl-5-rnethyl-2-rnercaptooxazole4-phenyl-S-methyI-Z-mercaptoimidazole Z-mercaptobenzothiazole4-phenyl-2-mercaptobenzothiazole 6-phenyl-2-mercaptobenzothiazole2-mercapto-tetrahydrobenzothiazole 2-mercapto-naphthothiazole The2-mercaptoarylenethiazoles and particularly 2-mercaptobenzothiazoleconstitute preferred species.

Solvents can often be used to an advantage in carrying out theinvention. Suitable solvents are the common inert organic solvents suchas chloroform, carbon tetrachloride, trichloroethylene, heptane andpetroleum ether.

Higher or lower temperatures than the reaction temperatures of theexamples can be employed. The reaction temperature is not critical, butit is desirable to use a temperature that will allow a reasonably rapidrate of reaction, so that the preparation can be carried outeconomically.

While certain representative embodiments and details are shown hereinfor the purpose of illustrating the invention, it will be apparent tothose skilled in the art that various modifications may be made thereinwithout departing from the spirit or scope of the invention.

We claim:

1. The method of preparing a thiosulfenamide which comprises reacting(a) one mole of an amine selected from the group consisting of (1) anamine represented by the formula in which R is selected from the groupconsisting of an alkyl of one to 8 carbon atoms, benzyl, cyclohexyl, 1-methyl-cyclohexyl, l-ethyl-cyclohexyl and l-methyl-cyclopentyl, and R isselected from the group consisting of hydrogen, an alkyl of one to 8carbon atoms, benzyl, cyclohexyl, 1-methyl-cyclohexyl,l-ethyl-cyclohexyl and l-methyl-cyclopentyl, (2) piperidine, (3)morpholine, (4) thiomorpholine, (5) 4-N-ethylpiperazine and (6)pyrrolidine with (b) one mole of an azole mercaptan selected from thegroup consisting of (1) a compound represented by the formula RCZ inwhich R is selected from the group consisting of hydrogen, an alkyl ofone to 4 carbon atoms and phenyl, R" is selected from the groupconsisting of hydrogen and an alkyl of one to 4 carbon atoms and Z isselected from the group consisting of sulfur, oxygen and NH, (2) 2-mercaptobenzothiazole, (3) 4-phenyl 2 mercaptobenzothiazole, (4)6-phenyl 2 mercaptobenzothiazole, (5) 2- mercaptotetrahydrobenzothiazoleand (6) Z-mercaptonaphthothiazole and with (c) one mole of a sulfurhalide of the formula in which n is an integer from 1 to 2 and X isselected from the group consisting of chlorine and bromine.

2. The method of claim 1 in which the amine is morpholine.

3. The method of claim 1 in which the azole mercaptan is2-mercaptobenzothiazole.

4. The method of claim 1 in which the sulfur halide is sulfurdichloride.

5. The method of claim 1 in which the amine is cyclohexylamine, theazole mercaptan is 2-mercaptobenzothiazole and the sulfur halide issulfur dichloride.

6. The method of claim 1 in which the amine is morpholine, the azolemercaptan is Z-mercaptobenzothiazole and the sulfur halide is sulfurmonochloride.

7. The method of claim 1 in which the amine is mor pholine, the azolemercaptan is Z-mercaptobenzothiazole and the sulfur halide is sulfurdichloride.

8. The method of claim 1 in which the amine is dimethylamine, the azolemercaptan is Z-mercaptobenzothiazole and the sulfur halide is sulfurdichloride.

9. The method of claim 1 in which the amine is piperidine, the azolemercaptan is 2-mercaptobenzothiazole and the sulfur halide is sulfurdichloride.

10. The process of reacting in substantially stoichiometric proportionsa 2-rnercapto-thiazole which may be substituted only in the 4 and 5positions solely by substituents composed of carbon and hydrogen free ofany but aromatic unsaturation, with an amine selected from the groupconsisting of morpholine, thiomorpholine, N-lower alkyl piperazine,pyrrolidine, and a piperidine containing besides the heterocyclicnitrogen only carbon and hydrogen, and a sulfur halide of the formula SX where n is an integer of from 1 to 2 and X is halogen, in the presenceof a hydrogen halide acceptor.

References Cited in the file of this patent UNITED STATES PATENTS1,661,998 Carson Mar. 6, 1928 2,060,428 Scott Nov. 10, 1936 2,259,164Jones Oct. 14, 1941 2,343,524 Blake Mar. 7, 1944 2,510,894 Kleiman June6, 1950 2,609,373 Beaver Sept. 2, 1952 2,747,005 Zerbe et al. May 22,1956 2,766,236 Harmon Oct. 9, 1956 2,835,670 Hardman May 21, 19582,850,496 Hardman Sept. 2, 1958 2,873,277 Sundholm Feb. 10, 1959 FOREIGNPATENTS 711,236 Great Britain June 30, 1954 OTHER REFERENCES Michaeliset al.: Ber. Dent. Chem. GeselL, vol. 28, pp. -167 (1895).

1. THE METHOD OF PREPARING A THIOSULFENAMIDE WHICH COMPRISES REACTING(A) ONE MOLE OF AN AMINE SELECTED FROM THE GROUP CONSISTING OF (1) ANAMINE REPRESENTED BY THE FORMULA
 6. THE METHOD OF CLAIM 1 IN WHICH THEAMINE IS MORPHOLINE, THE AZOLE MERCAPTAN IS 2-MERCAPTOBENZOTHIAZOLE ANDTHE SULFUR HALIDE IS SULFUR MONOCHLORIDE.